Vitamin and mineral supplements are among the most commonly used drugs in the U.S. Many consumers use supplements to prevent chronic diseases such as cancer, but with few exceptions, there is sparse evidence for either their benefits or risks. The goal of this study is to examine associations of various dietary supplements with lung and colorectal cancer incidence, using previously collected data from a large cohort study with a high proportion of supplement users. The primary aim is to investigate associations of supplemental vitamin C, vitamin E, calcium, and multivitamins over the 10-year period ending at baseline with the incidence of lung and colorectal cancers. Secondary objectives are to examine associations of intakes of 1) specific, less common vitamin, mineral, botanical, and other supplements (e.g., folate, beta carotene, selenium, fish oil/omega-3 fatty acids, fiber, and garlic supplements) and 2) non-steroidal anti-inflammatory drugs (NSAIDs) and lifestyle factors (e.g., diet, physical activity) with incidence of the lung and colorectal cancers and their interactions with supplements. Between 2000-2002, 77,738 men and women, aged 50-76 from western Washington State completed a baseline questionnaire that captured detailed information on use of 38 supplements over the previous 10 years, diet, physical activity, health history, and cancer risk factors. Supplement users were targeted in recruitment, therefore supplement use by cohort members is both high and of long duration: 79% were ever users of a supplement, and 66% used multivitamins, 46% used individual vitamin C, 47% used individual vitamin E, and 46% used calcium, typically for 5-8 of the previous 10 years. The cohort is being followed for lung and colorectal cancers by linkage to the western Washington SEER cancer registry, deaths by linkage to the Washington State death file, and out-migration from the SEER catchment area by linkage to the National Change of Address system. This proposal seeks funds to conduct analyses addressing the specific aims. We expect to identify 540 lung cancer cases after a mean follow-up of 4.3 years and 450 colorectal cancer cases after 5.3 years mean follow-up. The primary exposure would be average intake per day over the previous 10 years of the nutrient of interest (single supplements plus multivitamins) categorized as nonuse and tertiles among users, and all analyses will be adjusted for diet and other potential confounders and effect modifiers. The results of this study will augment the current body of scientific knowledge regarding associations of dietary supplements with lung and colorectal cancer risk and provide information to help guide the 100,000,000 adult Americans who take supplements, regardless of whether protective effects, no effects, or increased risks for specific supplements are found.